An introduction to vaccines and immunotherapy Flashcards
what are the principles of vaccination?
- vaccination aims to protect the individual and the population from the disease
- herd immunity
- immune system develops memory
is vaccination effective?
yes, leads to a massive drop in cases
an example is polio cases, which has been eradicated in most places following the polio vaccine (but not all).
types of vaccines
- living ones - natural or attenuated
- intact but non-living
- sub cellular fragments
- toxin based
- recombinant (DNA based)
describe living vaccines (natural)
Living vaccines can be natural or attenuated
Live vaccines aren’t popular, Vaccinia (for pox virus) is the only one that’s been in widespread use. Too risky, but now looking at knocking out genes to render live virus safe, eg new Rotavirus vaccine
describe living vaccines (attenuated)
attenuated = less damaging
Very successful - virus ones better than bacterial ones.
Example is BCG - cultured for 13 years then becomes safe attenuated version. Successful if maintained in non-human species culture. Doesn’t have to keep virulence genes needed to grow in human cell.
Problem: sometimes its virulence genes that make inflammatory response, and we need the immune response to kick off.
other examples: Hep A (also killed vaccine), yellow fever, tuberculosis, measles (80% effective)
describe dead vaccines
Range of effectiveness - rabies and Salk Polio are still pretty good
Sometimes issue – may not be as dead as think they are/ may induce disease state in v immunocompromised individuals
Less side effects from dead virus than attenuated - but, now being replaced by attenuated and subunit vaccines.
NB Salk polio vaccine, less effective than attenuated but also less risky. Since the chance of contracting polio has reduced this is making a comeback.
describe toxin-based vaccines
Toxoid: Usually bacterial exotoxin, which has been inactivated by heat or chemical action (eg by formalin). Active against toxin-induced illness.
Example: Clostridium tetani is a common soil bacterium that causes tetanus. Inactivate toxin with formalin and give patient 3 doses, and a boost every 10 years.
describe sub unit vaccines
Instead of whole virus. Use bits of them, e.g. take antigens.
Conjugate vaccines: Polysaccharides are usually not very immunogenic so conjugate to protein to get a better response (protein from same organism if poss, or give with tetanoid toxoid or diptheria). Get better response (IgG as well as IgM).
Polysaccharides don’t really generate good immune response.
Are vaccines Prophylactic or Therapeutic?
mix of both
Therapeutic = given once you get disease.
Prophylactic = before
examples of prophylactic vaccines
Smallpox;
Polio;
Tetanus (but needs booster!)
examples of therapeutic vaccines
Rabies: rare case
rabies vaccine
Louis Pasteur generated vaccine against rabies.
Took material from rabies infected tissue.
Rabies travels up nerves and sits in CNS tissue - develops very slowly and can generate an immune response whilst its travelling up.
Get a rabies shot very quickly after being bit (to be within window of opportunity)
Can be used prophylactically in high-risk groups.
But therapeutically in post-exposure.
Cancer immunotherapy - what is it?
a therapy used to treat cancer patients that involves or uses components of the immune system
some cancer immunotherapies consist of:
- antibodies that bind to and inhibit proteins expressed by cancer cells.
- vaccines and T cell infusions
Take WBC from patient and generate DC. Load with patient’s tumour lysate. And put back into patient.
Other types of immunotherapy for cancer: TILs and CARs.
TILs – tumour infiltrating lymphocytes cars = chimeric antibody receptors
what are adjuvants?
Adjuvants boost the immunogenicity of poor antigens (eg. some purified or recombinant proteins) and they initiate an inflammatory response.
They are usually responsible for the side-effects of vaccination (pain and swelling)
Recruit a lot immune cells, and some adjuvants have depot effect – retain immune cells at site. Recognise antigen better.
Examples: inorganic salts, liposomes, ISCOMs, bordetella perusis, interleukins, inferferons
vaccine administration - diff ways
By injection, intramuscular or cutaneous! Target Langerhan cells in the skin
Danger of needlestick: HIV
Needlephobia!
Jet injectors – compressed air. Like an air pistol, forces under air vaccine under skin (part has to be changed each time otherwise get cross contamination. (attempt to improve vaccine delivery) - now maybe disposable single –use cartridges
Microneedle arrays, polymer breaks down quickly. Can incorporate peptide / proteins in it. Put on arm. When dissolve, release peptide they are carrying, into the skin. Lots of little needles = inflammation (does job for you).
mucosal immunisation
Most vaccines aren’t delivered by injection. Mimics natural exposure route
Attenuated vaccines work well, killed vaccines don’t.
Vaccine needs to penetrate through gut wall, use adjuvant such as partially inactivated toxoids. Balance between ‘some’ and ‘too much’ inflammation. Needs to be able to get through gut wall, may need adjuvant to make site leaky through inflammation.
Need to overcome the tolerance which is usually associated with food antigens.
